Bictegravir-Tenofovir alafenamide-Emtricitabine ( Biktarvy ) - - PowerPoint PPT Presentation

Bictegravir-Tenofovir alafenamide-Emtricitabine (Biktarvy)

Prepared by: Brian R. Wood, MD David H. Spach, MD

Last Updated: December 31, 2019

Bictegravir-Tenofovir Alafenamide-Emtricitabine (Biktarvy)

INSTI NRTI NRTI

Biktarvy

[bik-TAR-vee]

Bictegravir-Tenofovir alafenamide-Emtricitabine

Dose: 1 tablet once daily with or without food 50 mg 25 mg 200 mg

Bictegravir-Tenofovir alafenamide-Emtricitabine (Biktarvy)

• Single-Tablet Regimen Components:

Bictegravir: 50 mg Tenofovir alafenamide: 25 mg Emtricitabine: 200 mg

• Dosing: 1 pill daily with or without food
• With Renal or Hepatic Impairment
• Do not initiate if estimated CrCl <30 mL/min
• Do not initiate with severe hepatic impairment (Child-Pugh C)
• Pregnancy: insufficient data
• Common Adverse Events (≥5%)
• Diarrhea (6%), nausea (5%), and headache (5%)

• Phase 2 Trial in Treatment-Naïve Adults
• GS-141-1475: BIC + TAF-FTC versus DTG + TAF-FTC
• Phase 3 Trials in in Treatment-Naïve Adults
• GS-380-1489: BIC-TAF-FTC versus DTG-ABC-3TC
• GS-380-1490: BIC-TAF-FTC versus DTG + TAF-FTC
• Phase 3 Trials in Adults with Virologic Suppression
• GS-380-1844: Switch to BIC-TAF-FTC or stay on DTG-ABC-3TC
• GS-380-1878: Switch to BIC-TAF-FTC or stay on boosted PI + NRTIs
• GS-380-1844: 1961: Switch to BIC-TAF-FTC in women
• GS-380-1844 and GS-380-1878: Impact of Archived M184V Mutation

Bictegravir-Tenofovir alafenamide-Emtricitabine Summary of Key Studies

Bictegravir-Tenofovir alafenamide-Emtricitabine

INITIAL THERAPY

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Design

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

Bictegravir 75 mg QD + TAF-FTC

(n = 65)

Dolutegravir 50 mg QD + TAF-FTC

(n = 33)

GS-141-1475: Study Design

• Background: Randomized, double-blind, placebo-

controlled, phase 2 study evaluating the efficacy and safety of bictegravir versus dolutegravir as part of antiretroviral therapy for treatment-naïve adults with HIV

• Inclusion Criteria
• Age > 18
• Antiretroviral-naïve
• CD4 count >200 cells/mm3
• HIV RNA ≥1,000 copies/mL
• eGFR >70 mL/min
• Genotypic sensitivity to TAF and FTC
• No hepatitis B or C
• Not pregnant
• No AIDS-defining condition within 30 days

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Results

Weeks 24 and 48: Virologic Response by FDA Snapshot Analysis

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

97 97 94 91 20 40 60 80 100

24 weeks 48 weeks HIV RNA < 50 copies/mL (%)

Bictegravir + TAF-FTC Dolutegravir + TAF-FTC

63/65 31/33 63/65 30/33

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Adverse Events

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

Most Frequent Adverse Events in Either Study Group Bictegravir + TAF-FTC

(n = 65)

Dolutegravir + TAF-FTC

(n = 33)

Any adverse event 55 (85%) 22 (67%) Diarrhea 8 (12%) 4 (12%) Nausea 5 (8%) 4 (12%) Arthralgia 4 (6%) 2 (6%) Fatigue 4 (6%) 2 (6%) Headache 5 (8%) 1 (3%)

No serious treatment-related adverse events occurred in either arm. 1 participant (with history of atopic dermatitis) in the bictegravir arm discontinued due to urticaria.

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Laboratory Abnormalities

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

Most frequent laboratory abnormalities in either study group Bictegravir + TAF-FTC

(n = 65)

Dolutegravir + TAF-FTC

(n = 33)

Any laboratory abnormality 28 (44%) 15 (47%) Creatinine kinase elevation 8 (13%) 3 (9%) AST elevation 6 (9%) 1 (3%) Fasting glucose elevation 5 (8%) 4 (13%) ALT elevation 4 (6%) 0 (0%) LDL elevation 4 (6%) 3 (9%) Amylase elevation 3 (5%) 2 (6%)

Median decrease from baseline in estimated creatinine clearance: 7.0 mL/min in the bictegravir arm and 11.3 mL/min in the dolutegravir arm.

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Virologic Rebound and Resistance

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

Participants with Viral Rebound Meeting Protocol-Defined Criteria for Genotype Resistance Testing Study arm Resistance detected Participant 1 Bictegravir + TAF-FTC None Participant 2 Dolutegravir + TAF-FTC None Participant 3* Dolutegravir + TAF-FTC T97A

*This participant discontinued the study at week 48 due to non-adherence.

Bictegravir versus Dolutegravir, each with TAF-FTC

GS-141-1475: Conclusions

Source: Sax PE, et al. Lancet HIV. 2017;4:e154-e160.

Interpretation: “Bictegravir plus emtricitabine and tenofovir alafenamide and dolutegravir plus emtricitabine and tenofovir alafenamide both showed high efficacy up to 24 weeks. Both treatments were well

• tolerated. Administration of bictegravir, a novel, potent, once-daily INSTI

designed to improve on existing INSTI options with the backbone of emtricitabine and tenofovir alafenamide, might provide an advantage to patients.”

BIC-TAF-FTC vs. DTG-ABC-3TC as Initial Therapy

GS-380-1489

BIC-TAF-FTC versus DTG-ABC-3TC as Initial Therapy

GS-380-1489: Design

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

Bictegravir-TAF-FTC

(n = 314)

Dolutegravir-ABC-3TC

(n = 315)

GS-380-1489: Study Design

• Background: Randomized, double-blind, active-

controlled, phase 3 study evaluating the efficacy and safety of bictegravir-tenofovir alafenamide- emtricitabine versus dolutegravir-abacavir- lamivudine for treatment-naïve adults with HIV

• Inclusion Criteria
• Age >18
• Antiretroviral-naïve (or ≤10 days of treatment)
• HIV RNA ≥500 copies/mL
• eGFR ≥50 mL/min
• HLA B*5701 negative
• No chronic HBV infection
• Regimens
• Bictegravir-TAF-FTC (50/25/200 mg)
• Dolutegravir-ABC-3TC (50/600/300 mg)

BIC-TAF-FTC versus DTG-ABC-3TC as Initial Therapy

GS-380-1489: Baseline Characteristics

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

Study GS-380-1489 Baseline Characteristics Characteristic BIC-TAF-FTC

(n = 314)

DTG + TAF-FTC

(n = 315)

Median age, years (range) 31 (18-71) 32 (18-68) Male, % 91 90 Black or African descent, % 36 36 HIV RNA >100,000 copies/mL, % 17 16 CD4 count <200 cells/mm3, % 11 10 Median CrCl, mL/min 125.9 123.0

Abbreviations: CrCl = creatinine clearance

BIC-TAF-FTC versus DTG-ABC-3TC as Initial Therapy

GS-380-1489: Results

Week 48 Virologic Response (Intention-to-Treat Analysis)

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

92.4 93.0 20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Dolutegravir-ABC-3TC

No treatment-emergent resistance to any study drug occurred

290/314 293/315

BIC-TAF-FTC versus DTG-ABC-3TC as Initial Therapy

GS-380-1489: Adverse Events

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

Treatment Emergent Adverse Events (AE’s >5%) Through Week 48 BIC-TAF-FTC

(n = 314)

DTG-ABC-3TC

(n = 315)

Diarrhea, % 13 13 Headache, % 11 14 Nausea, % 10 23 Fatigue, % 6 9 Arthralgia, % 4 6 Insomnia, % 4 6 Change in eGFR (mL/min)

• 10.5
• 10.8

BIC-TAF-FTC versus DTG-ABC-3TC for Initial Therapy

GS-380-1489: Results

Change in Markers of Proximal Tubulopathy at 48 Weeks

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

0.6 13.6

• 23.0

6.2 19.9

• 18.1
• 30
• 20
• 10

10 20 30 Urine Albumin/ Creatinine Retinonl Binding Protein Beta-2-Microglobulin/ Creatinine Median % Change from Baseline

Bictegravir-TAF-FTC Dolutegravir-ABC-3TC

BIC-TAF-FTC versus DTG-ABC-3TC for Initial Therapy

GS-380-1489: Results

Change in Bone Mineral Density at 48 Weeks

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

• 0.83
• 0.78
• 0.60
• 1.02
• 1.5
• 1.0
• 0.5

0.0 0.5

Spine Hip

Median % Change from Baseline

Bictegravir-TAF-FTC Dolutegravir-ABC-3TC

BIC-TAF-FTC versus DTG-ABC-3TC for Initial Therapy

GS-380-1489: Results

Change in Lipids at 48 Weeks

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

13 7 5 9 11 4 5 3 5 10 15 20 TC LDL HDL TG Median Change from Baseline (mg/dL)

Bictegravir-TAF-FTC Dolutegravir-ABC-3TC

BIC-TAF-FTC versus DTG-ABC-3TC for Initial Therapy

GS-380-1489: Conclusions

Source: Gallant J, et al. Lancet. 2017;390:2063-72.

Interpretation: “At 48 weeks, coformulated bictegravir, emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent

• resistance. Bictegravir, emtricitabine, and tenofovir alafenamide was safe

and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide does not require HLA B*5701 testing and provides guideline-recommended treatment for individuals co-infected with HIV and hepatitis B, this regimen might lend itself to rapid or same-day initiation of therapy in the clinical setting.”

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490: Week 48 Results

BIC-TAF-FTC versus DTG + TAF-FTC as Initial Therapy

GS-380-1490: Design

Source: Sax PE, et al. Lancet. 2017;390:2073-82.

Bictegravir-TAF-FTC

(n = 320)

Dolutegravir + TAF-FTC

(n = 325)

GS-380-1490: Study Design

• Background: Randomized, double-blind, active-

controlled, phase 3 study evaluating the efficacy and safety of bictegravir-tenofovir alafenamide- emtricitabine versus dolutegravir plus tenofovir alafenamide-emtricitabine for treatment-naïve adults with HIV

• Inclusion Criteria
• Age >18
• Antiretroviral-naïve (or ≤10 days of treatment)
• HIV RNA ≥500 copies/mL
• eGFR ≥30 mL/min
• Regimens
• Bictegravir-TAF-FTC (50/25/200 mg)
• Dolutegravir (50 mg) + TAF-FTC (25/200 mg)

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 48): Baseline Characteristics

Source: Sax PE, et al. Lancet. 2017;390:2073-82.

Study 1490 Baseline Characteristics Characteristic BIC-TAF-FTC

(n = 320)

DTG + TAF-FTC

(n = 325)

Median age, years (range) 33 (27-46) 34 (27-46) Male, % 88 89 Black or African descent, % 30 31 HIV RNA >100,000 copies/mL, % 21 17 CD4 count <200 cells/mm3, % 14 10 HBV coinfection, % 3 2 HCV coinfection, % 2 2 Median CrCl, mL/min 120.4 120.6

Abbreviations: CrCl = creatinine clearance

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 48): Results

Week 48 Virologic Response (Intention-to-Treat Analysis)

Source: Sax PE, et al. Lancet. 2017;390:2073-82.

89 93

20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Dolutegravir + TAF-FTC

No participant discontinued due to lack of efficacy in either arm No treatment-emergent resistance to any study drug occurred

286/320 302/325

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 48): Adverse Events

Source: Sax PE, et al. Lancet. 2017;390:2073-82.

Treatment Emergent Adverse Events (AE’s >5%) Through Week 48 BIC-TAF-FTC

(n = 320)

DTG + TAF-FTC

(n = 325)

Headache, % 13 12 Diarrhea, % 12 12 Nausea, % 8 9 Fatigue, % 6 8 Arthralgia, % 5 3 Insomnia, % 5 4 Change in eGFR

• 7.3 mL/min
• 10.8 mL/min

Abbreviations: eGFR = estimated glomerular filtration

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 48): Conclusions

Source: Sax PE, et al. Lancet. 2017;390:2073-82.

Interpretation: “At 48 weeks, virological suppression with the bictegravir regimen was achieved and was non-inferior to the dolutegravir regimen in previously untreated adults. There was no emergent resistance to either regimen. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen.”

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490: Week 96 Results

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 96): Results

Week 96 Virologic Response (Intention-to-Treat Analysis)

Source: Stellbrink HJ , et al. Lancet. 2019;6:e364-e372.

84 86

20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Dolutegravir + TAF-FTC

269/320 281/325

BIC-TAF-FTC vs. DTG + TAF-FTC as Initial Therapy

GS-380-1490 (Week 96): Conclusions

Source: Stellbrink HJ , et al. Lancet. 2019;6:e364-e372.

Interpretation: “These week 96 data support bictegravir, emtricitabine, and tenofovir alafenamide as a safe, well tolerated, and durable treatment for people living with chronic HIV.”

Bictegravir-Tenofovir alafenamide-Emtricitabine

SWITCH STUDIES

Switch from DTG-ABC-3TC to BIC-TAF-FTC in Adults with Virologic Suppression

GS-380-1844

Switch from DTG-ABC-3TC to BIC-TAF-FTC

GS-380-1844: Design

Source: Molina JM, et al. Lancet HIV. 2018;5:e357-e365.

Switch Regimen

Bictegravir-TAF-FTC

(n = 282)

Maintain Regimen

DTG-ABC-3TC

(n = 281)

GS-380-1844: Study Design

• Background: Randomized, phase 3, multicenter,

double-blind, active-controlled study evaluating the efficacy and safety of switching adults with HIV and viral suppression to BIC-TAF-FTC versus continuing DTG-ABC-3TC

• Inclusion Criteria
• Age >18
• HIV RNA <50 copies/mL
• eGFR >50 mL/min for at least 3 months
• No history of treatment failure
• Taking DTG-ABC-3TC or DTG + ABC-3TC
• No documented or suspected resistance to

DTG, ABC, 3TC, FTC, or TAF

• HCV infection allowed
• HBV infection not allowed

Switch from DTG-ABC-3TC to BIC-TAF-FTC

GS-380-1844: Results

Week 48 Virologic Response (Intention-to-Treat Analysis)

Source: Molina JM, et al. Lancet HIV. 2018;5:e357-e365.

94 95

20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Dolutegravir-ABC-3TC

At 48 weeks, proportion with HIV RNA >50 copies/mL not statistically different: 1% BIC vs <1% DTG 5 participants met criteria for virologic failure and resistance testing (3 BIC, 2 DTG); no resistance found

264/282 267/281

Switch from DTG-ABC-3TC to BIC-TAF-FTC

GS-380-1844: Results

Most Common Treatment-Related Adverse Events by 48 Weeks

Source: Molina JM, et al. Lancet HIV. 2018;5:e357-e365.

Most Common Treatment-Related Adverse Events (AE’s) BIC-TAF-FTC

(n = 282)

DTG-ABC-3TC

(n = 281)

AE’s leading to study drug discontinuation 2 1 Headache, % 2 3 Diarrhea, % 1 1 Abnormal dreams, % <1 2 Fatigue, % <1 1 Nausea, % 2 Insomnia, % 3

Switch from DTG-ABC-3TC to BIC-TAF-FTC

GS-380-1844: Conclusions

Source: Molina JM, et al. Lancet HIV. 2018;5:e357-e365.

Interpretation: “The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for

• ngoing treatment of HIV-1 infection.”

Switch from Boosted PI + 2 NRTI’s to BIC-TAF-FTC with Viral Suppression

GS-380-1878

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Design

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

Switch Regimen Bictegravir-TAF-FTC

(n = 290)

Maintain Regimen Boosted PI + 2 NRTI’s

(n = 287)

GS-380-1878: Study Design

• Background: Randomized, phase 3, multicenter,
• pen-label switch study evaluating the efficacy and

safety of switching adults with viral suppression taking a boosted PI plus 2 NRTI’s to BIC-TAF-FTC

• Inclusion Criteria
• Age >18
• HIV RNA <50 copies/mL for ≥6 months
• On stable antiretroviral regimen for ≥6 months
• No history of treatment failure
• No prior treatment with an INSTI
• eGFR >50 mL/min
• HBV and HCV allowed
• Taking atazanavir or darunavir (each boosted by

ritonavir or cobicistat) + TDF-FTC or ABC-3TC

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Baseline Characteristics

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

Study GS-380-1878 Baseline Characteristics Characteristic BIC-TAF-FTC

(n = 290)

Boosted PI + 2 NRTI’s

(n = 287)

Median age, years (range) 48 47 Male, % 84 82 Black or African descent, % 27 25 Hispanic/Latino, % 21 16 Median CD4, cells/mL 617 626 HBV coinfection, % 8 6 HCV coinfection, % 5 5 Median eGFR, mL/min 107 105 Baseline TDF-FTC, ABC-3TC, % 84, 16 85, 15 Baseline DRV, ATV, % 57, 43 54, 46

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Results

Week 48 Virologic Response (Intention-to-Treat Analysis)

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

92 89

20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Boosted PI + 2 NRTI's

Primary outcome of HIV RNA >50 copies/mL at 48 weeks: 2% each arm

267/290 255/287

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Adverse Events

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

Treatment Emergent Adverse Events Through Week 48 BIC-TAF-FTC

(n = 290)

Boosted PI + 2 NRTI’s

(n = 287)

Headache, % 12 4 Diarrhea, % 8 8 Nasopharyngitis, % 7 12 URI, % 7 8 Back pain, % 5 6 Arthralgia, % 4 5 Change in eGFR

• 4.3 mL/min

0.2 mL/min

Abbreviations: eGFR = estimated glomerular filtration

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Results

Change in Lipids at 48 Weeks

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

1 3

• 6

5 3 1 4

• 8
• 6
• 4
• 2

2 4 6 8 TC LDL HDL TG Median Change from Baseline (mg/dL)

Bictegravir-TAF-FTC Boosted PI + 2 NRTI's

Switch from Boosted PI to BIC-TAF-FTC

GS-380-1878: Conclusions

Source: Daar E, et al. Lancet HIV. 2018;5:e347-e356.

Interpretation: “Fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide might be a safe and efficacious alternative to continued boosted protease inhibitor therapy in adults with HIV-1 infection.”

Switch to BIC-TAF-FTC in Women with Virologic Suppression

GS-380-1961

Switch to BIC-TAF-FTC in Women with Virologic Suppression

GS-380-1961: Design

Source: Kityo C, et al. J Acquir Immune Defic Syndr. 2019;82:321-8.

Switch Regimen

Bictegravir-TAF-FTC

(n = 234)

Maintain Regimen INSTI or PI-Based Regimen

(n = 236)

GS-380-1844: Study Design

• Background: Randomized, phase 3, multicenter,
• pen label, active-controlled study evaluating the

efficacy and safety of switching women with HIV and viral suppression to BIC-TAF-FTC versus continuing their baseline regimen

• Inclusion Criteria
• Women aged >18
• HIV RNA <50 copies/mL for at least 12 weeks
• *Taking EVG/c/TAF/FTC, EVG/c/TDF/FTC, or

ATV/r + TDF/FTC

• eGFR >50 mL/min
• No suspected resistance to study drugs
• Using contraception if child-bearing potential
• Chronic hepatitis B or C allowed

*Regimens: 53% EVG/c/TAF/FTC and 42% EVG/c/TDF/FTC

Switch to BIC-TAF-FTC in Women with Virologic Suppression

GS-380-1961: Results

Source: Kityo C, et al. J Acquir Immune Defic Syndr. 2019;82:321-8.

95.7 95.3

20 40 60 80 100 HIV RNA <50 copies/mL (%)

Bictegravir-TAF-FTC Maintain Regimen

Switch to BIC-TAF-FTC in Women with Virologic Suppression

GS-380-1961: Conclusions

Source: Kityo C, et al. J Acquir Immune Defic Syndr. 2019;82:321-8.

Interpretation: “Fixed-dose combination bictegravir- emtricitabine-tenofovir alafenamide provides a safe and efficacious option for ongoing treatment of HIV in women. This study contributes important data on safety, tolerability, and outcomes of antiretroviral therapy among women living with HIV.”

BIC-TAF-FTC Switch Studies (1844 and 1878)

Impact of Archived M184V Mutation

Switching to Bictegravir-TAF-FTC with Archived M184V

Studies 1844 and 1878: Design

Source: Andreatta K, et al. J Antimicrob Chemo. 2019;74:3555-64.

1844 & 1878: Analysis of Switch Studies

• Background: Preexisiting resistance data were

assessed from 2 phase 3 studies that analyzed switching antiretroviral regimens in adults with suppressed HIV RNA levels (for ≥6 months) to bictegravir-tenofovir alafenamide-emtricitabine (BIC-TAF-FTC) versus continuing regimen

• Analysis for Resistance Criteria
• Historical genotypes
• Retrospective proviral archived DNA genotype
• Resistance data obtained for 95% (543/570) of

participants who switched to BIC-TAF-FTC *56% boosted Darunavir

Switch Regimen Bictegravir-TAF-FTC (n=570) Maintain Regimen 1844: Dolutegravir + ABC-3TC (n=285) 1878: Boosted PI* + 2NRTIs (n=281)

Switching to Bictegravir-TAF-FTC with Archived Resistance

Studies 1844 and 1878: Results

Pre-existing resistance substitutions and virologic outcomes at 48 weeks

Source: Andreatta K, et al. J Antimicrob Chemo. 2019;74:3555-64.

Percentage with HIV RNA <50 copies/mL by baseline resistance mutation BIC-FTC-TAF

(n = 543)

Common NRTI Substitutions M184V/I 96.3% (52/54) K65R/N 100.0% (7/7) Any TAM 95.8% (46/48) 1 or 2 TAM’s 94.3% (33/35) 3 or more TAM’s 100.0% (13/13) Primary INSTI Substitutions T97A 100% (9/9) E92G or Y143H or S147G or Q148H 100% (4/4)

Switching to Bictegravir-TAF-FTC with Archived M184V

Studies 1844 and 1878: Key Points

Source: Andreatta K, et al. J Antimicrob Chemo. 2019;74:3555-64.

• Baseline M184V/I in 10% of switch group (BIC-TAF-FTC)
• 96% (52/54) with archived M184V had HIV RNA <50

copies/mL for up to 48 weeks on BIC-TAF-FTC

Switching to Bictegravir-TAF-FTC with Archived M184V

Studies 1878 and 1844: Conclusions

Source: Andreatta K, et al. J Antimicrob Chemo. 2019; pii:dkz347.[Epub ahead of print]

Interpretation: “Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. These results indicate that BIC/FTC/TAF is an effective treatment option for suppressed patients, including those with evidence of archived NRTI resistance.”

Bictegravir 10-day Dose-Ranging Monotherapy

GS-141-1219

Bictegravir 10-day Dose-Ranging Monotherapy

GS-141-1219: Design

Source: Gallant JE, et al. J Acquir Immune Defic Syndr. 2017;75:61-6.

Bictegravir: 5 mg QD

(n = 4)

Bictegravir: 25 mg QD

(n = 4)

Bictegravir: 50 mg QD

(n= 4)

Placebo

(n = 4)

Bictegravir: 100 mg QD

(n = 4)

GS-141-1219: Study Design

• Background: Randomized, double-blind, dose-

ranging, placebo-controlled, 10-day, phase 1b study to evaluate antiviral activity, safety, and pharmacokinetics of the INSTI bictegravir in adults with HIV

• Inclusion Criteria (n = 20)
• Antiretroviral-naïve or
• Antiretroviral-experienced but INSTI-naïve
• Age: between 18 and 65
• CD4 >200 cells/mm3
• HIV RNA between 10,000 and 400,000 copies/mL
• Treatment Arms
• Bictegravir: 5, 25, 50, or 100 mg daily
• Placebo: daily

Bictegravir 10-day Dose-Ranging Monotherapy

GS-141-1219: Results

Baseline to Day 11: Change in Baseline HIV RNA Level

Source: Gallant JE, et al. J Acquir Immune Defic Syndr. 2017;75:61-6

• 1.45
• 2.08
• 2.06
• 2.43

0.12

• 3.0
• 2.5
• 2.0
• 1.5
• 1.0
• 0.5

0.0 0.5

5 mg 25 mg 50 mg 100 mg Placebo

Change in HIV RNA from Baseline (Log10 copies/mL) Bictegravir (once daily dosing)

Bictegravir 10-day Dose-Ranging Monotherapy

GS-141-1219: Conclusions

Source: Gallant JE, et al. J Acquir Immune Defic Syndr. 2017;75:61-6

Interpretation: “Bictegravir is a novel, potent, unboosted integrase strand transfer inhibitor (INSTI) that demonstrated rapid, dose-dependent declines in HIV-1 RNA after 10 days of monotherapy. Bictegravir was well tolerated, and displayed rapid absorption and a half-life supportive of

• nce-daily therapy in HIV-infected subjects.”

Acknowledgment

The National HIV Curriculum is an AIDS Education and Training Center (AETC) Program supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $800,000 with 0% financed with non-governmental sources. This project is led by the University of Washington’s Infectious Diseases Education and Assessment (IDEA) Program.

The content in this presentation are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government.